EMBR-13. FAVORABLE OUTCOMES IN CHILDREN WITH PINEOBLASTOMA TREATED WITH RISK-ADAPTED CRANIOSPINAL IRRADIATION AND CHEMOTHERAPY: RESULTS AND MOLECULAR ANALYSIS FROM THE SJYC07 AND SJMB03 TRIALS
Bibliographic record
Abstract
Pineoblastoma (PB) is an aggressive embryonal tumor that has been uniformly treated with high-dose craniospinal irradiation (CSI). Herein, we describe patients diagnosed with PB treated on 2 multi-center, prospective trials with risk-adapted radiation regimens. Patients <3yr received chemotherapy with/without focal irradiation (SJYC07). Patients ≥3yr received risk-adapted CSI (23.4Gy for localized disease, 36–39.6Gy for metastatic) and chemotherapy (SJMB03). DNA methylation was performed using Infinium MethylationEPIC BeadChip and profiled on DKFZ molecularneuropathology2.0 classifier. 40 patients were enrolled (SJMB03=28; SJYC07=12) with 6.07yr median age (range: 0.37–20.4) and 3.8yr median follow-up (range: 0.37–13.1). Twenty-two were stratified as high-risk (HR). All 28 SJMB03 patients received CSI; 6 SJYC07 patients received focal RT and 6 were not irradiated. All but one patient received chemotherapy (parental refusal). On SJMB03, 10/11 non-HR patients receiving 23.4Gy CSI survived without progression (5yr-PFS 100%) as compared to 8/17 HR patients (5yr-PFS 56.3 ± 12.4%). On SJYC07, 11/12 progressed (5yr-PFS 8.3 ± 8.0%). 23/40 tumors (58%) were methylation profiled into the following categories: PBgroupB (N=11), PBgroupA(N=2), pineal parenchymal tumor (N=1), choroid plexus tumor (CPT) (subclass pediatric B) (N=1), with 6 samples having calibrated score <0.9 (associated with medulloblastomagroup3=4, CPT=1, PBgroupB=1, no-match=2). All patients with PB-B were aged ≥3yr with 67% (8/12) surviving progression-free. Patients <3yr had PBgroupA/medulloblastoma/CPT and only 14% (1/7) survived progression-free. Non-metastatic PB in children ≥3yr has excellent survival with average-risk medulloblastoma therapy. The poor survival of young children and HR-PB might be explained by underlying molecular heterogeneity, and clustering of pineal tumors with MBgroup3 or CPT warrants further investigation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".